Many medically significant biological processes are mediated by proteins participating in signal transduction pathways that involve G-proteins and/or second messengers such as cAMP. The membrane protein gene superfamily of G-protein coupled receptors (GPCRs) include a wide range of biologically active receptors, such as hormone, viral, growth factor and neuroreceptors. GPCRs have been characterized as having seven putative transmembrane domains (designated TM1, TM2, TM3, TM4, TM5, TM6, and TM7), which are believed to represent transmembrane α-helices connected by extracellular or cytoplasmic loops. Most G-protein coupled receptors have single conserved cysteine residues in each of the first two extracellular loops which form disulfide bonds that are believed to stabilize functional protein structure. G-protein coupled receptors can be intracellularly coupled by heterotrimeric G-proteins to various intracellular enzymes, ion channels and transporters. Different G-protein α-subunits preferentially stimulate particular effectors to modulate various biological functions in a cell.
Seven-transmembrane domain GPCRs (aka serpentine receptors) are involved in signaling in response to a diverse array of agonists. In fact, the body uses seven membrane-spanning serpentine receptors for an astounding variety of biological signaling functions. Serpentine receptors do not depend upon receptor dimerization in order to transduce signals across the plasma membrane. Instead, single receptor molecules will change their three-dimensional steric configuration in response to ligand binding. This steric shift affects the configuration of the cytoplasmic domains of the receptor (i.e., the loops of receptor protein that protrude into the cytoplasm).
One member of the serpentine receptor subfamily is CYT28, the complete 3021 bp cds for which has been deposited in GenBank (Accession No.: AF166382; GI No.: 6006810).
Given the importance of GPCRs in biological and disease processes, a clear need exists for further in vivo characterization, which may aid in the identification and discovery of therapeutics and treatments useful in preventing, ameliorating or correcting dysfunctions or diseases.